RNA interference (RNAi) is a process where introduction of dsRNA into a cell causes destruction of RNA in a sequence-specific manner (see, D. Baulcombe, Curr. Biol., 12:R83 (2002); Hutvagner et al., Curr. Opin. Genet. Dev., 12:225 (2002)) RNAi has been observed in plants, Neurospora, flies, protozoans, and mice. Available data show that double-stranded (ds) RNA serves as the initial trigger of RNA interference and upon recognition, is processed by the Dicer RNAse into short fragments of 21 nucleotides (nt) in length. These short interfering (si)RNAs are then incorporated into a dsRNA-induced silencing complex (RISC) to guide cycles of specific RNA degradation.
Recent work has established that in higher plants targeted degradation of RNA occurs as a natural antiviral response, rather than simply being a response to artificially introduced or artificially induced dsRNA. Work by Dougherty and co-workers shows that virus infection is able to trigger RNA silencing of a homologous virus-derived transgene in transgenic tobacco (see, Lindbo et al., Plant cell, 5:1749-1759 (1993)). The activation of silencing is accompanied by recovery of the host from the initially virulent infection so that the new growth is both symptom and virus-free and is highly resistant to a secondary challenge by the same virus. This type of RNA-mediated virus resistance (RMVR), demonstrated conclusively for a number of dicot plant species with a variety of viruses (see, Waterhouse et al., Trends Plant Sci., 4:452-457 (1999)), is also functional in monocot plants (see, Ingelbrecht et al., Plant Physiol., 119:1187-1188 (1999)). This phenomenon, termed RNA silencing, has been shown to occur via a similar mechanism as RNA interference. Many plant RNA viruses have been found to encode efficient suppressors of RNA silencing. One such suppressor is the 2b protein encoded by cucumber mosaic cucumovirus (CMV). The idea that Cmv2b functions as a suppressor of host defense was first proposed based in the finding that Cmv2b is essential for the development of CMV disease symptoms in its hosts (see, Ding et al., EMBO J, 14:5762 (1995)). Previous analyses also indicated that the Cmv2b gene represents a newly evolved gene as compared to the other four CMV genes (see, Ding et al., Virology, 198:593-601 (1994)), suggesting that the Cmv2b gene is a viral adaptation to the RNA silencing antiviral defense in plants. Available evidence also shows that suppression of RNA silencing plays central role in the induction of viral disease in plants (see, Ding et al., Curr. Opin. Biotechnol., 11(2):152-156).
It is well established that cellular and humoral adaptive immunity based on peptide recognition are defenses employed against viruses by animals. However, little is known about other antiviral defenses in animals. In order to develop effective treatments for viral infections in mammals, it is necessary to identify and characterize these additional modes of antiviral defense. This invention fulfills these and other related needs.